title: Effect of miltefosine on erythrocytes.
abstract: BACKGROUND
  Miltefosine, an alkylphosphocholine drug with antiparasite, antibacterial, antifungal and antineoplastic potency, is the only oral drug that can be used to treat visceral and cutaneous leishmaniasis. The effect of miltefosine is at least partially due to triggering of apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Eryptosis may be triggered following increase of cytosolic Ca(2+)-level ([Ca(2+)]i). The present study explored, whether miltefosine elicits eryptosis.
  
  
  METHODS
  Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3-fluorescence.
  
  
  RESULTS
  A 48 h exposure to miltefosine (≥ 4.9 μM) was followed by significant decrease of forward scatter and significant increase of annexin-V-binding. The effect was paralleled by significant increase of [Ca(2+)]i. The annexin-V-binding following miltefosine treatment was significantly blunted in the nominal absence of extracellular Ca(2+).
  
  
  CONCLUSIONS
  Miltefosine stimulates eryptosis, an effect at least partially due to stimulation of Ca(2+) entry.
authors.affiliation: Department of Physiology, University of Tuebingen, Gmelinstr. 5, 72076 Tuebingen, Germany.
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Janin
authors.initials: J
authors.lastname: Jacobi
authors.forename: Majed
authors.initials: M
authors.lastname: Abed
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000890:Anti-Infective Agents / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D010718:Phosphatidylserines; D010767:Phosphorylcholine; C039128:miltefosine
keywords: Calcium; Cell volume; Eryptosis; Miltefosine; Phosphatidylserine